Allylic oxidation of compounds bearing active methylene groups to corresponding .alpha.,.beta.-unsaturated carbonyl compounds is an important organic reaction having applications in a variety of fields ranging from agricultural products to pharmaceuticals and the like. Allylic oxidation reactions have traditionally been performed using a wide variety of chromium(VI) compounds. Among other common oxidants are potassium permanganate, manganese dioxide, ruthenium compounds, selenium dioxide, copper and its compounds. Catalytic oxidation using oxygen or air is known whereby metal compounds and N-hydroxy cyclic imides have been used as catalysts. Most of these procedures are not environmentally friendly, and typically suffer from one or more additional drawbacks such as unsatisfactory yields, use of large excess of the oxidant(s), harsh reaction conditions, use of toxic chemicals, difficulty in scaling up, generation of copious amount of toxic waste, use of expensive reagents etc. and therefore, are not industrially feasible processes for bulk production.
The use of tert-butyl hydroperoxide in combination with some of the oxidants such as chromium, ruthenium, and copper compounds has afforded allylically oxidized product(s) under relatively milder conditions but the reaction still utilizes the toxic metal compounds, and/or often requires use of toxic solvents such as benzene and the process produces toxic waste making the process eco unfriendly. Also, because of the incomplete and/or partial conversion, the product is often contaminated with the starting material and, quite often, complex mixture of products comprised of alcohols, ketones, hydroperoxides etc. is obtained.
Hence, a continuing need exists for a simple, efficient and cost effective as well as eco-friendly procedure for selectively effecting the allylic oxidation of organic compounds bearing an active methylene group, particularly .DELTA..sup.5 -steroids into corresponding .alpha.,.beta.-unsaturated ketones.
In our previous patent (Marwah et al, U.S. Pat. No. 5,869,709) we have described a new cost effective, simple procedure for allylic oxidation of a wide variety of organic compounds, utilizing sodium periodate or periodic acid and aqueous tert-butyl hydroperoxide. The procedure was developed successfully and is being utilized for the industrial production of one of our commercial products. However during commercial production it was observed that the only drawback associated with this process was production of large amount of aqueous waste containing salts of various lower oxidation stages of iodine such as iodates, iodides etc.
The present patent deals with a simple, eco-friendly, cost effective procedure based on green chemistry to the extent feasible, for the allylic oxidation of a wide variety of organic compounds having at least two allylic hydrogens into corresponding .alpha.,.beta.-unsaturated carbonyl compounds.
Sodium hypochlorite is a well-known oxidizing agent and a household bleaching agent and disinfectant and is easily and cheaply available under various brand names such as clorox. The commercially available aqueous solution of sodium hypochlorite comes with .about.5.0-12.5% available oxidant (w/v, .about.0.7 M-1.75 M). Concentration is expressed as % available chlorine since half the chlorine in bleach is present as sodium chloride. In the chemical synthesis, sodium and calcium hypochlorite have been successfully used to oxidize aldehydes into corresponding acids (--CHO into COOH) preferably in presence of a phase transfer catalyst, and secondary alcohols into ketones (--CHOH into --C.dbd.O) in presence of acetic acid, and primary alcohols to esters, ethers to esters, and thioethers to sulfoxides. Hypochlorites are effective, although infrequently utilized reagents for epoxidation of enones and polycyclic arenes. They are also reagents for N-chlorination, oxidative coupling, degradation reactions etc. and reactive methylene groups have occasionally been oxidized to the corresponding gem-diols. (Encyclopedia of reagents for organic synthesis; Editor-in-Chief: Leo A, Paquette, John Wiley & Sons 1995, p.966-68, 4580-86; Skarzewski J. and Siedlecka R., Organic Preparation and Procedures International, 24 (1992) 623-647 and Fieser's Reagent in Organic Synthesis, John Wiley & Sons, 1 1084 (1967); 4 456 (1974); 5 617 (1975); 6 543 (1977); 7 337 (1979); 8 461 (1980); 9 430 (1981); 10 365 (1982); 11 107 & 487 (1984); 15 293 (1990); 16 308 (1992); 17 316 (1994); 18 84 & 335 (1999); and 19 313 (1999)). It has also been reported that a methylene or methyl group attached to an aromatic ring can be oxidized to carboxylic acids provided the ring contains also an acetyl group. (Fieser's Reagent in Organic Synthesis 1, 1084) However, to the best of our knowledge, metal hypochlorites have never been used for a one step allylic oxidation of allylically activated methylene group to corresponding .alpha.,.beta.-unsaturated carbonyl compound (&gt;CH.sub.2 into &gt;C.dbd.O).